Search

We conducted a phase Ib study to examine the safety of a combination of carbon-ion RT (CIRT) with durvalumab (MEDI4736; AstraZeneca) in patients with locally advanced cervical cancer. This was an open-label, single-arm study with a modified 3 + 3 design. Patients with newly diagnosed histologically proven locally advanced cervical cancer were enrolled. All patients received 74.4 Gy of CIRT in 20 fractions and concurrent weekly cisplatin (chemo-CIRT) at a dose of 40 mg/m2. Durvalumab was administered (1500 mg/body) at weeks two and six. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs), including dose-limiting toxicity (DLT). All three enrolled patients completed the treatment without interruption. One patient developed hypothyroidism after treatment and was determined to be an SAE. No other SAEs were observed. The patient recovered after levothyroxine sodium hydrate treatment. None of the AEs, including hypothyroidism, were associated with DLT in the present study. All three patients achieved complete responses within the CIRT region concerning treatment efficacy. This phase 1b trial demonstrates the safety of combining chemo-CIRT and durvalumab for locally advanced cervical cancer in the early phase. Further research is required as only three patients were included in this study.

The pearlside Maurolicus stehmanni is one of the most abundant mesopelagic fishes off southeastern Brazil and plays a key role in the regional ecosystem. However, its early life history remains poorly understood. This study examined the M. stehmanni early life stages, from eggs to juveniles, including all developmental changes in external morphology. Larvae are simple in morphology and lack specialised larval structures. Notochord flexion begins at ~ 5.15 mm BL and larvae ≥ 5.95 mm BL are flexed. The relative growth of seven measured larval characters (head length, body depth, snout length, eye diameter, pre-dorsal length, pre-ventral length, and pre-anal length) have transition points (allometric inflexion points), indicating biphasic growth patterns which are likely related to shifts in habitat use, feeding, and behaviour. Larval development is similar to that of other Maurolicus species. The relatively fast development of the fins, photophores, swimbladder, and pigmentation suggests a precocious adoption of a micronektonic lifestyle in the mesopelagic environment. This article is protected by copyright. All rights reserved.

Objectives Tacrolimus may be administered to pregnant women with lupus nephritis in Japan if considered therapeutically beneficial, but supporting data are limited. We assessed the safety and effectiveness of tacrolimus before, during, and after pregnancy in women with lupus nephritis receiving tacrolimus. Methods This was an ad hoc analysis of data from a post-marketing surveillance study of tacrolimus in patients with lupus nephritis in Japan. Pregnancy outcomes, nephritis status, and adverse events were assessed for up to 2 years postpartum. Results Data were available for 23 births in 21 patients (two patients had two births each). Tacrolimus for lupus nephritis was continued during 11 births in nine patients (during and after pregnancy) and discontinued in 12 patients (when pregnancy was known or when approaching delivery). Renal function was generally maintained in patients who gave birth while receiving tacrolimus; however, there were cases of increased urine protein and decreased renal function over 2 years. There were no unexpected adverse events/safety concerns. Conclusions These data from clinical practice suggest that tacrolimus is a valid treatment option for lupus nephritis in fertile women in Japan and, with careful monitoring, pregnant women with lupus nephritis may continue their tacrolimus treatment.

Du Bois's interest in the Japanese empire points us in the direction of examining non-Western imperial policies and discourses and how they relate to racialization. For Du Bois, Japan was an exemplar of a nonwhite empire. This chapter reconstructs a Du Boisian conception of race that identifies it closely with ethnicity, against the belief that the African-American intellectual held on to a merely biological conception of race. I argue that his thought evolved towards a social-construction approach in which race must be understood historically and in particular global contexts. By analyzing Japan's policies and discourses around the boundaries of the Japanese, I explicate how Japan carried out a process of self-racialization owing to its dialectical relationship with the West. It also racialized its colonial subjects in a process of in-group delineation according to Japan's imperial imperatives. The case of the Japanese empire demonstrates how a global/transnational approach to racialization is valuable. It also evinces how white supremacy and universalism are not the only logics of imperialism. Moreover, it shows that Du Bois believed white supremacy could be transcended. However, Du Bois was too idealistic about Japan's empire, ignoring how oppressive nonwhite imperial rulers can be toward their subjects even when there are phenotypical similarities between them.

The Hokkaido Eastern Iburi Earthquake (M = 6.7) occurred on Sep. 6, 2018 in the southern part of Central Hokkaido, Japan. Since Paleogene, this region has experienced the dextral oblique transpression between the Eurasia and North American (Okhotsk) Plates and the subsequent collision between the Northeast Japan Arc and the Kuril Arc due to the oblique subduction of the Pacific Plate. This earthquake occurred beneath the foreland fold-and-thrust belt of the Hidaka Collision zone developed by the collision process, and is characterized by its deep focal depth (~ 37 km) and complicated rupture process. The reanalyses of controlled source seismic data collected in the 1998–2000 Hokkaido Transect Project revealed the detailed structure beneath the fold-and-thrust belt, and its relationship with the aftershock activity of this earthquake. Our reflection processing using the CRS/MDRS stacking method imaged for the first time the lower crust and uppermost mantle structures of the Northeast Japan Arc underthrust beneath a thick (~ 5–10 km) sedimentary package of the fold-and-thrust belt. Based on the analysis of the refraction/wide-angle reflection data, the total thickness of this Northeast Japan Arc crust is only 16–22 km. The Moho is at depths of 26–28 km in the source region of the Hokkaido Eastern Iburi Earthquake. Our hypocenter determination using a 3D structure model shows that most of the aftershocks are distributed in a depth range of 7–45 km with steep geometry facing to the east. The seismic activity is quite low within the thick sediments of the fold–thrust belt, from which we find no indication on the relationship of this event with the shallow (

IntroductionConcurrent chemoradiotherapy is considered the standard treatment strategy for locally advanced cervical cancer. Most recent reports indicate that patients with bulky tumours or adenocarcinoma subtypes have poorer local control. Carbon-ion radiotherapy (CIRT) with the concurrent use of chemotherapy has shown promising results in such cases of difficult-to-treat uterine cervical cancer. Programmed death-ligand 1 (PD-L1) upregulation was observed in tumour tissue samples from patients who had undergone CIRT. Thus, a combination of CIRT and anti-PD-L1 antibody may suppress metastasis by activating antitumour immune response, in addition to exhibiting strong local effects.ObjectiveWe will assess the safety and tolerability (primary endpoint) of the concomitant use of durvalumab, an anti-PD-L1 antibody, with CIRT and weekly cisplatin for locally advanced cervical cancer.Methods and analysisThis study is a non-randomised, open-label, prospective phase 1b study. Up to 10 patients with histologically proven uterine cervical cancer at stage IIB, IIIA, IIIB, IIIC1 or IVA as per International Federation of Gynecology and Obstetrics (2018) staging will be enrolled. All patients will receive CIRT of 74.4 Gy relative biological effectiveness in 20 fractions over 5 weeks (four fractions per week). Weekly cisplatin at a dose of 40 mg/m2will be administrated up to five times. Durvalumab at a dose of 1500 mg/body will be administrated at weeks 2 and 6. Safety and tolerability will be evaluated based on the frequency of dose-limiting toxicities until 92 days after CIRT starts. Patients will be followed-up strictly as per the scheduled protocol for 1 year after CIRT initiation.Ethics and disseminationThe Human Research Ethics Committees of QST Hospital (#C21-002) and Chiba University (#2021006) have approved this study protocol. The findings will be published in peer-reviewed journals and presented at scientific conferences.Trial registration numberJapan Registry of Clinical Trials (jRCT2031210083), registered on 12 May 2021.

This article provides a critical assessment of comparative sociology of race and ethnicity (CSRE). It underscores leading themes and conceptual paradigms that shape current studies in cross-cultural, cross-national, cross-regional, and transnational perspectives on race. It highlights cutting-edge work in the field by examining some cardinal concerns in studies by region, and it points to lacunae that must be addressed by future research. I argue that studies of race in sociology have been anchored in concepts, theories, and paradigms that are heavily derived from U.S.-based experiences and models for too long. I urge for more studies of race and ethnicity that are not limited by this dominance of U.S.-based perspectives or by those that privilege Western contexts such as Europe. This is because there is no cogent reason to assume that race and its intertwined concept of ethnicity are primarily or originally U.S.- or Western-grounded phenomena. The article concludes by pointing to some conceptual and methodological notions that ought to guide future research in the area.

This conclusion discusses a shift in genomics scholarship from disinterest in race to a commitment to understanding race. It describes the issues and misconceptions emerging from this new race-related genomics research. Most of the writers in the field of race and genomics have slowly but inevitably come to the realization that, as social scientists have long known, the disconnect between the data produced by scientific studies and the way these results are interpreted and appropriated by the general public has all the allure of cognitive dissonance. Most scholars start the story of this disconnect with the advent of the very public Human Genome Project under the Clinton administration. The discoveries of the Human Genome Project failed to completely transcend race. After examining both Western and non-Western cases, this chapter illuminates six main points related to the genomics-race interface that should be highlighted in the future study of this area.

This introduction discusses perspectives on race after the genomics revolution, which posed a serious question to those who had accepted the synthetic or nonnatural foundations of the idea and the phenomenon of race. Some argued that the new genomics data affirmed either the existence of biologically distinctive human subgroups or the need to use these new findings to address apparent health disparities along “racial” lines. Although some scholars have argued that we should discard the idea of race altogether, the fact remains that it is a widely used concept in social reality. Due to the tensions between biological, medical, and genetic understandings of race, there is no term that properly describes the distinction between a genetically rooted racial concept and a socioculturally rooted racial concept. A new concept, clusivity, is proposed here to make analytical distinctions for further explorations of “race” in the postgenomic age.

Hyperuricemia is a risk factor for adverse renal outcomes in patients with chronic kidney disease. This study investigated the effect of uric acid on renal function in a community-based population.We used a nationwide database of 165 847 subjects (aged 29-74, male 40%) who participated in the annual 'Specific Health Check and Guidance in Japan' checkup between 2008 and 2010; we examined the relationship between serum uric acid levels at baseline and 2-year change in the estimated glomerular filtration rate (eGFR) obtained by using the Japanese equation.After adjusting for possible confounders, the eGFR change was inversely correlated with uric acid at baseline. In the multivariable analysis, the decline in eGFR was significantly more rapid in subjects with the slight increase in uric acid (males ≥5.7 mg/dL, females ≥4.4 mg/dL), and the risk for incidental renal insufficiency (eGFR60 mL/min/1.73 m(2)) was increased at uric acid of ≥6.3 mg/dL in males and ≥5.5 mg/dL in females, compared with the lowest quintile. The multiple linear regression analysis revealed that the effect of uric acid on eGFR changes was significant, especially in females, those with proteinuria and diabetes and those without alcohol consumption.This study showed that serum uric acid is independently associated with a more rapid decline of eGFR and incident renal insufficiency, and that a slight increase within the normal range of serum uric acid might be a risk for renal damage in the general population.

Albuminuria is a known risk factor for cardiovascular events and premature deaths. However, the association between urinary albumin excretion and mortality is unknown in the Japanese population. To clarify this, we conducted a community-based longitudinal study.This study included 3,445 registered Japanese subjects (mean age 62.6 years), with a 7-year follow-up. Albuminuria was defined as a urine albumin-creatinine ratio (ACR) ≥30 mg/g in the morning spot urine.Subjects with albuminuria (n = 514, 14.9 %) were older and showed a higher prevalence of hypertension, obesity, and diabetes and lower values of estimated glomerular filtration rate (eGFR) than those without albuminuria (n = 2931, 85.1 %). During the follow-up, 138 subjects died. A Kaplan-Meier analysis showed that all-cause mortality significantly increased along with the increase in urine albumin excretion (log-rank test, P 0.001). The subjects with albuminuria showed a significantly higher mortality rate than those without albuminuria (7.4 vs. 3.4 %; log-rank test, P 0.001). A Cox proportional hazard model analysis after adjusting for possible confounders showed that albuminuria was an independent risk factor for all-cause and cardiovascular mortality (hazard ratio [HR] 1.69, 95 % confidence interval [CI] 1.12-2.56 and HR 2.27, 95 % CI 1.10-4.70, respectively) but not for noncardiovascular mortality. These associations were preserved after excluding subjects with high ACR (≥300 mg/g).Albuminuria was a risk factor for all-cause and cardiovascular mortality in the Japanese population. To detect subjects with a high risk for premature death, measuring urinary albumin excretion might be useful.

AIM To investigate the long term effects of cardiac events on renal function, a prospective study of patients with acute myocardial infarction was conducted. METHODS A total of 137 patients with acute myocardial infarction were followed for 1 year. The change of estimated glomerular filtration rate (eGFR) in cardiac patients was compared with that in background-matched controls, and the factors associated with eGFR changes were analyzed. RESULTS The eGFR decrease was much larger after myocardial infarction, from 73.7 ± 1.9 ml/min/1.73 m2 (mean ± SEM) at baseline to 64.7 ± 1.7 at 1 year, (p < 0.001), compared with that of controls (from 72.8 ± 1.2 to 72.1 ± 1.3, p = 0.305). Multiple regression analysis showed that eGFR change was associated negatively with age, baseline eGFR, proteinuria, and positively with the administration of angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, but not the severity of cardiac damage and comorbidities. Longitudinal analysis 1 year before and 2 years after myocardial infarction showed that eGFR decrease was larger during baseline and 6 months after the event (-7.0 ± 1.0). CONCLUSIONS Renal decline was rapid after myocardial infarction and was affected by clinical characteristics of patients. Careful follow-up of renal function is recommended to prevent the progression of renal and cardiac disease.

What accounts for varying forms of adaptation of immigrants to host countries? Despite their common ethnic origin, Korean immigrants demonstrate very different adaptation pa erns in Japan and the United States. By elucidating the importance of different national peculiarities in racial ideology, this article argues that Korean immigrants are racialized differently given different circumstances and structural conditions in these two countries. Employing a cross-national comparison focusing on a single ethnic group, this study shows that cultural and racial similarities between immigrants and the mainstream of the host society do not guarantee smooth assimilation. This article concludes that in the long run, differences in modes of incorporation are more relevant to immigrant adaptation than visible racial or cultural differences between the immigrants and the mainstream of the host society. Spanish ¿Cómo se explican las diversas formas de adaptación de inmigrantes en los países receptores? A pesar de su origen étnico común, los inmigrantes coreanos han mostrado patrones de adaptación muy diferentes en Japón y los Estados Unidos. Al mostrar la importancia de las diferentes peculiaridades nacionales en la ideología racial, este artículo argumenta que los inmigrantes coreanos son racializados diferencialmente de acuerdo a las distintas circunstancias y las condiciones estructurales en estos dos países. A través de una comparación transnacional centrada en un solo grupo étnico, este estudio muestra que las similitudes raciales y culturales entre los inmigrantes y la mayoría de la sociedad de acogida, no garantizan una fácil asimilación. En este artículo se concluye que, en el largo plazo, las diferencias en los modos de incorporación son más relevantes para la adaptación de los inmigrantes que las visibles diferencias raciales / culturales entre los inmigrantes y la generalidad de la sociedad receptora. French Comment expliquer les formes variables de l'adaptation des immigrants dans le pays hôte ? En dépit de leur origine ethnique commune, les immigrants coréens ont montré des modes d'adaptation très différents au Japon et aux Etats-Unis. En montrant l'importance de certaines particularités nationales pour l'idéologie raciale, cet article soutient que ces immigrants coréens sont racialement différenciés en fonction des situations et des conditions structurelles différentes dans ces deux pays. Par le biais d'une comparaison transnationale portant sur un seul groupe ethnique, ce e étude montre que les similarités culturelles et raciales entre les immigrants et la société-hôte traditionnelle ne sont pas les garantes d'une assimilation aisée. Cet article conclut que, sur le long-terme, les modes d'incorporation sont plus importants pour l'adaptation des immigrants que les différences raciales/culturelles visibles entre les immigrants et la société traditionnelle de l'Etat-hôte.

Cross polarization-magic angle spinning (CPMAS) is the most used experiment for solid-state NMR measurements in the pharmaceutical industry, with the well-known variant RAMP-CPMAS its dominant implementation. The experimental work presented in this contribution focuses on the entangled effects of the main parameters of such an experiment. The shape of the RAMP-CP pulse has been considered as well as the contact time duration, and a particular attention also has been devoted to the radio-frequency (RF) field inhomogeneity. (13)C CPMAS NMR spectra have been recorded with a systematic variation of (13)C and (1)H constant radiofrequency field pair values and represented as a Hartmann-Hahn matching two-dimensional map. Such a map yields a rational overview of the intricate optimal conditions necessary to achieve an efficient CP magnetization transfer. The map also highlights the effects of sweeping the RF by the RAMP-CP pulse on the number of Hartmann-Hahn matches crossed and how RF field inhomogeneity helps in increasing the CP efficiency by using a larger fraction of the sample. In the light of the results, strategies for optimal RAMP-CPMAS measurements are suggested, which lead to a much higher efficiency than constant amplitude CP experiment.

To examine the relationship between dialysis modality and prognosis in Japanese patients, we conducted a prospective multicenter observational study. We recruited 83 background-matched peritoneal dialysis (PD) and 83 hemodialysis (HD) patients (average age, 64.9 years; men, 53.6%; diabetic patients, 22.9%; median duration of dialysis, 48 months in all patients) and followed them for 5 years. During the follow-up period, 27 PD patients (16 cardiovascular and 11 non-cardiovascular deaths) and 27 HD patients died (14 cardiovascular and 13 non-cardiovascular deaths). There were 8 PD patients switched to HD, and 6 PD patients received renal transplantation. Kaplan-Meier analysis revealed that the crude survival rate was not significantly different at the end of 5 years (PD 67.5% versus 67.5%, log-rankP=0.719). The difference in cardiovascular and non-cardiovascular mortalities between PD and HD was not statistically significant. Multivariate Cox analysis showed that the independent predictors for death were age and serum albumin levels, but not the dialysis modality. This study showed that the overall mortality was not significantly different between PD and HD patients, which suggests that dialysis modality might not be an independent factor for survival in Japanese patients.

Background. A cluster of proinflammatory cytokines plays an important role in the development of various renal diseases, and the expression of these cytokines is genetically modified. To examine the association between polymorphisms of proinflammatory cytokine genes and albuminuria, a cross-sectional study was conducted in the general population. Methods. Single nucleotide polymorphisms (SNPs) in six proinflammatory cytokine genes, including interleukin (IL)-1b, IL-6, IL-8, tumor necrosis factor (TNF)-a ,C C chemokine ligand 1 (CCL1) and monocyte chemoattractant protein-1 (MCP-1), were genotyped in 2927 Japanese subjects. Urine albumin–creatinine ratio (UACR) was measured in morning spot urine samples. Results. Albuminuria (UACR � 30 mg/g) was significantly associated with the A/A 1 A/G genotype at rs2069852 in the IL-6 gene (P ¼ 0.01) and the A/A genotype at rs228269 in the CCL1 gene (P ¼ 0.002). Multivariate analysis with adjustment for traditional risk factors showed that these genotypes independently predicted albuminuria [odds ratio (OR) 1.782, 95% confidence interval (CI) 1.171–2.712, P ¼ 0.007 for the A/A 1 A/G genotype at rs2069852 in IL-6, and OR 1.432, 95% CI 1.128–1.770, P ¼ 0.003 for the A/A genotype at rs228269 in CCL1]. The prevalence of albuminuria and the UACR were increased along with the increase of risk genotypes. Conclusions. This study revealed that SNPs in the IL-6 and CCL1 genes were associated with albuminuria, and the combination of these genotypes had an additive effect on the prevalence and severity of albuminuria. This indicates that genetic factors influencing inflammatory responses may affect the development of renal injury in the Japanese general population.

Rationale: Hypertrophic pachymeningitis (HP) is an uncommon, life-threatening disease that is seen in elderly patients with antineutrophil cytoplasmic antibody (ANCA) positivity. Proteinase-3 (PR3)-ANCA-positive HP has not been reported in adolescents. Here, we report the first case of adolescent PR3-ANCA-positive HP successfully treated with immunosuppressive therapy. Patient concerns: A 14-year-old female presented with fullness and pain in her right ear unresponsive to antibiotics. Laboratory tests showed an elevated C-reactive protein and PR3-ANCA positivity. Computed tomography and magnetic resonance imaging revealed mastoiditis in the right temporal bone. Surgical biopsy revealed severe fibrosis and prominent inflammatory-cell infiltration. She received prednisolone and methotrexate therapy, and then underwent a right mastoidectomy. Five months later, she developed headache, dysarthria, and multiple cranial nerve palsies. Further imaging revealed enhancement and thickening of the right hemispheric dura. Diagnosis: PR3-ANCA-positive HP. Interventions: She was successfully treated with steroid pulse therapy for 3 days, followed by high doses of prednisolone and intravenous cyclophosphamide. Outcome: The treatment resulted in significant improvement of her symptoms, laboratory data, and radiologic findings. Lessons: PR3-ANCA-positive HP can present not only in the elderly, but also in adolescence, and prompt diagnosis and treatment with immunosuppressive therapy is vital.

Rationale:Dialysis-related amyloidosis (DRA) can present rheumatic manifestations in patients on long-term hemodialysis. Typical articular symptoms with DRA involve carpal-tunnel syndrome, effusion in large joints, spondyloarthropathy, or cystic bone lesions, which are usually with non-infla

Glomerular and tubular damage are important factors in the development of renal insufficiency. However, the interaction of these factors is largely unknown in the non-diabetic Japanese population. To clarify the relationship between renal insufficiency and both glomerular and tubular damage, we conducted a community-based study using albuminuria and urine beta 2-microglobulin as markers of glomerular and tubular damages, respectively.Subjects of this study were 2816 non-diabetic individuals40 years old in Takahata, Japan. The urine albumin-creatinine ratio (UACR) and urine beta 2-microglobulin-creatinine ratio (UBCR) were assessed from single spot urine. The glomerular filtration rate (eGFR) was estimated using the abbreviated MDRD equation with a Japanese coefficient.The prevalence of albuminuria (UACR20 mg/ g in men and30 mg/g in women), increased UBCR (300 microg/g) and renal insufficiency (eGFR60 mL/ min/1.73 m(2)) were 21.0%, 12.5% and 21.7%, respectively, and there was only a small overlap between the three. The mean eGFR was significantly lower in subjects with macroalbuminuria (UACR200 mg/g in men and300 mg/g in women) and increased UBCR. No urinary abnormalities were observed in 71.7% of the 611 subjects with renal insufficiency, and were more common in young, women and the non-hypertensive population. The 1-year decline of eGFR was greatest in subjects with an overlap of macroalbuminuria and increased UBCR.This study indicated that only a small part of renal insufficiency accompanied increased urine albumin or beta 2-microglobulin in the non-diabetic Japanese population. The combination of macroalbuminuria and increased urine beta 2-microglobulin might predict faster renal deterioration.

Multidrug resistance-related protein 1 (MRP1), an ATP-binding cassette transporter encoded by the ABCC1 gene, is expressed in many tissues, and functions as an efflux transporter for glutathione-, glucuronate- and sulfate-conjugates as well as unconjugated substrates. In this study, the 31 exons and their flanking introns of ABCC1 were comprehensively screened for genetic variations in 153 Japanese subjects to elucidate the linkage disequilibrium (LD) profiles and haplotype structures of ABCC1 that is necessary for pharmacogenetic studies of the substrate drugs. Eighty-six genetic variations including 31 novel ones were found: 1 in the 5'-flanking region, 1 in the 5'-untranslated region (UTR), 20 in the coding exons (9 synonymous and 11 nonsynonymous variations), 4 in the 3'-UTR, and 60 in the introns. Of these, eight novel nonsynonymous variations, 726GT (Trp242Cys), 1199TC (Ile400Thr), 1967GC (Ser656Thr), 2530GA (Gly844Ser), 3490GA (Val1164Ile), 3550GA (Glu1184Lys), 3901CT (Arg1301Cys), and 4502AG (Asp1501Gly), were detected with an allele frequency of 0.003. Based on the LD profiles, the analyzed regions of the gene were divided into five LD blocks (Blocks -1 and 1 to 4). The multiallelic repeat polymorphism in the 5'-UTR was defined as Block -1. For Blocks 1, 2, 3 and 4, 32, 23, 23 and 13 haplotypes were inferred, and 9, 7, 7 and 6 haplotypes commonly found onor = 10 chromosomes accounted foror = 91% of the inferred haplotypes in each block. Haplotype-tagging single nucleotide polymorphisms for each block were identified to capture the common haplotypes. This study would provide fundamental and useful information for the pharmacogenetic studies of MRP1-dependently effluxed drugs in Japanese.

Serum uric acid level is regulated by gender, dietary habit, genetic predisposition, and renal function, and is associated with the development of renal and cardiovascular diseases. This study prospectively investigated the association between serum uric acid levels and mortality in a community-based population. Three thousand four hundred and eighty-seven subjects regardless of the antihyperuricemic medication (45 % male; mean age 62 years old) from the Takahata town in Japan participated in this study and were followed up for 8 years (median 7.5 years). We examined the association between serum uric acid levels at baseline and the all-cause and cardiovascular mortality, respectively, in this population. One hundred seventy-nine subjects died during the follow-up period, with 49 deaths attributed to cardiovascular causes. Kaplan–Meier analysis revealed that the all-cause mortality was significantly higher along with the increase in serum uric acid levels at baseline among female (Log-rank P

Glimepiride, a sulfonylurea hypoglycemic agent, is metabolized by cytochrome P450 2C9 (CYP2C9) which is known to have genetic polymorphisms. To examine the effects of CYP2C9 genetic polymorphisms on the safety and efficacy of glimepiride in patients with type 2 diabetes, the responses to the glimepiride were measured in Japanese type 2 diabetic patients with the different CYP2C9 genotype. The reduction in the HbA 1c was significantly larger ( P CYP2C9*1 / *3 subjects than among the CYP2C9*1 / *1 subjects. The long-term observations of 2 patients with a CYP2C9*1 / *3 suggested that subjects with a CYP2C9*1 / *3 respond well to glimepiride during the initial phase of treatment, but 1 patient have shown the weight gain over the long-term treatment. The pharmacokinetic study showed that the area under the concentration-time curve for glimepiride in the CYP2C9*1 / *3 subjects was approximately 2.5-fold higher than that of the CYP2C9*1 / *1 subjects. The intrinsic clearance of glimepiride by the CYP2C9*3 enzyme was lower than that by the CYP2C9*1 enzyme. These results suggested that the lower hydroxylation activity of glimepiride in the subject with type 2 diabetes and CYP2C9*1 / *3 led to a marked elevation in the plasma concentrations of glimepiride and a stronger pharmacological effect of glimepiride.

透析患者の皮膚〓痒症は高頻度でQOLを下げる重要な合併症である. 今回, 透析患者の〓痒と皮膚乾燥の関連について肌水分計とかゆみスケールを用いて検討した. 対象は維持血液透析患者124名 (男性72名・女性52名, 平均年齢63歳, 平均透析歴102か月, 慢性糸球体腎炎72名・糖尿病28名) と, 健常者28名 (男性16名, 女性12名, 平均年齢61.5歳) で, 肌水分計 (ナショナルDM-RI) を用いて角層水分量を, かゆみスケールを用いて〓痒度を測定し検討した. 透析患者の角層水分量は健常者より少なく, 非シャント肢にくらべてシャント肢の方で少なかった. 皮膚〓痒症は37.5%に認められ, 角層水分量と〓痒度は負の相関を示した. 角層水分量の多い群と少ない群の比較では, 多い群で年齢が高く, 少ない群で〓痒度とリンが高かった. 皮膚〓痒の原因はさまざまな因子の関与が考えられるが, 今回の検討では皮膚乾燥との関連が認められた. 今後, 皮膚保湿などのスキンケアを実施し, 皮膚乾燥の変化と〓痒に対する効果について検討する予定である.

Forty-eight single nucleotide variations, including 27 novel ones, were found in the 5'- regulatory region, all of the exons and their surrounding introns of CYP2C19 in 253 Japanese subjects (134 diabetic patients and 119 healthy volunteers). Identified novel variations were as follows: -2772G>A, 2767_-2760delGGTGAACA, -2720T>C, -2547delG, -2545G>T, -2545_-2544 delGC, and -2040C>T in the enhancer region; -778C>T, -777G>A, -529G>C, -189C>A, and -185A>G in the promoter region; 151A>G (S51G), 481G>C (A161P), 986G>A (R329H), 1078G>A (D360N), and 1119C>T (D373D) in the exons, and IVS1+128T>A, IVS3+163G>A, IVS4+271A>G, IVS5-49A>G, IVS6-210C>T, IVS6-196T>A, IVS6-32T>A, IVS7+84G>A, IVS7-174C>T, and IVS8+64C>T in the introns. Since we found no significant differences in the variation frequencies between healthy volunteers and diabetic patients, the data for all subjects were treated as one group in further analysis. The allele frequencies were 0.265 for IVS6-196T>A, 0.045 for -2772G>A and -2720T>C, 0.024 for -2040C>T, 0.014 for IVS7-174C>T, 0.010 for -529G>C, 0.006 for IVS1+128T>A and 481G>C (A161P), 0.004 for -2767_-2760delGGTGAACA and IVS6-210C>T, and 0.002 for the other 17 variations. In addition, the two known nonsynonymous single nucleotide polymorphisms, 681G>A (splicing defect, (*)2 allele) and 636G>A (W212X; (*)3 allele) were detected at 0.267 and 0.128 frequencies, respectively. No variation was detected in the known binding sites for constitutive androstane receptor and glucocorticoid receptor. Linkage disequilibrium analysis showed several close linkages of variations throughout the gene. By using the variations, thirty-one haplotypes of CYP2C19 and their frequencies were estimated. Our results would provide fundamental and useful information for genotyping CYP2C19 in the Japanese and probably other Asian populations.

Aim: The present study was conducted to clarify the type and frequency of verbal communication between caregivers and elderly residents in geriatric care facilities. The relationship of this verbal communication was studied in terms of the caregivers talking to elderly residents and the utterances issued by the elderly residents. The attributes of the elderly residents were also studied. Methods: There were 35 eldery residents living in three metropolitan geriatric care facilities. Observations were made of caregivers talking to elderly residents and of elderly residents talking to caregivers in order to conduct a content analysis that categorized the types of verbal communication observed. A statistical analysis of the relationship between the frequency and duration of verbal communication and attributes of the elderly residents was carried out. Results: There were two category types of talking to elderly residents by a caregiver: ‘talking to elicit the ‘activities of daily living (ADL)-related behavior/performance or physical functioning’ (type I: instrumental communication) and ‘talking to facilitate psychosocial life activities’ (type II: affective communication), of which the former accounted for 75.9%. The number of spontaneous utterances from elderly residents was very low, with most utterances being responses to caregivers talking to them. There was a tendency for utterances from the elderly residents to increase as the total time of being talked to by caregiver increased (r = 0.47, P

A series of novel lipophilic vitamin C derivatives, 6-O-acyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acids possessing a branched-acyl chain of varying length from C(8) to C(16) (6-bAcyl-AA-2G), were evaluated as topical prodrugs of ascorbic acid (AA) with transdermal activity in a human living skin equivalent model. The permeability of 6-bAcyl-AA-2G was compared with those of the derivatives having a straight-acyl chain (6-sAcyl-AA-2G). Out of 10 derivatives of 6-sAcyl-AA-2G and 6-bAcyl-AA-2G, 6-sDode-AA-2G and 6-bDode-AA-2G exhibited most excellent permeability in this model. Measurement of the metabolites permeated from the skin model suggested that 6-bDode-AA-2G was mainly hydrolyzed via 6-O-acyl AA to AA by tissue enzymes, while 6-sDode-AA-2G was hydrolyzed via 2-O-alpha-D-glucopyranosyl-L-ascorbic acid to AA. The former metabolic pathway seems to be advantageous for a readily available source of AA, because 6-O-acyl AA, as well as AA, is able to show vitamin C activity.

Introduction: Polymyositis (PM) is a type of autoimmune, inflammatory myopathy. IgG4-related disease (IgG4-RD) is a recently recognized disease entity characterized by elevated serum IgG4 levels and IgG4+ plasma-cell infiltration of various organs. However, several reports have described cases of other diseases that present with those features, suggesting the importance of careful differential diagnosis. Herein, we report the first case of PM with elevated serum IgG4 levels and IgG4+ plasma cells in the muscles, mimicking IgG4-RD. A 73-year-old woman visited our hospital because of proximal muscle weakness of both thighs. Her blood test showed high levels of serum creatinine kinase, aldolase, and IgG4. Magnetic resonance imaging of the thighs showed muscle edema. Needle electromyography showed findings typical of myositis. Histological analysis of her left quadriceps revealed infiltration of IgG4+ plasma cells as well as CD8+ T cells. Scattered necrotic and regenerating muscle fibers with no specific findings for IgG4-RD (storiform fibrosis and obliterative phlebitis) were typical for PM. We diagnosed her condition as PM and treated her with 40 mg/day of prednisolone that decreased levels of muscle enzymes and improved muscle weakness. Conclusion: Our case indicated that PM could present with high serum IgG4 levels and IgG4+ plasma-cell infiltration, mimicking IgG4-RD. Although the mechanism of IgG4 elevation in such PM is unclear, our case highlights the necessity to recognize that high serum IgG4 levels and IgG4+ plasma-cell infiltration in organs are not specific for IgG4-RD.

Background Hypertension and proteinuria are risk factors for adverse renal outcomes in patients with chronic kidney disease. This study investigated the associations of blood pressure and proteinuria on renal function in a community-based population. Methods We analyzed data from a nationwide database of 141,514 subjects who participated in the annual "Specific Health Check and Guidance in Japan" checkup in 2008 and 2010. The study subjects were aged between 29 and 74 years, and the cohort comprised 40% men. We examined relationships between blood pressure levels, proteinuria at baseline, and the 2-year change in the estimated glomerular filtration rate (eGFR), which was determined using the Japanese equation. Results After adjusting for possible confounders, the change in the eGFR was inversely correlated with systolic blood pressure (SBP), but not diastolic blood pressure (DBP), at baseline, irrespective of the presence of proteinuria. Compared with the lowest SBP sixtile (≤118mm Hg), eGFRs declined significantly at SBPs ≥ 134mm Hg in subjects with proteinuria, while eGFRs declined significantly at SBPs ≥ 141mm Hg in those without proteinuria. At the same SBPs, renal function decline was faster and the risk for incident renal insufficiency was higher in subjects with proteinuria compared with those without proteinuria. Conclusions This study showed that a difference in SBP, but not DBP, is independently associated with a rapid eGFR decline in the general Japanese population, and that the association of SBP on the decline of renal function was greater in subjects with proteinuria compared with those without proteinuria.

Morphological and osteological development of the flathead,Percophis brasiliensis, is described based on specimens collected from southeastern Brazilian waters. Identification of larvae was based on pigment pattern and meristic counts. Distinct melanophores were present on the bottom of the hindbrain, between the bases of the pelvic fins and on the bases of the pectoral fins. Within the family Percophididae onlyPercophis brasiliensis has 57 myomeres, which result in the larvae having an elongated body form. The larval pigment pattern and structure of the caudal complex suggest that the subfamilies Percophinae and Bembropinae are phylogenetically close, while the Hemerocoetinae belong to an advanced group within the family.

Morphological development of barracudas (Sphyraena guachancho andS. tome) is described, based on larval and juvenile specimens collected in the southeast Brazilian Bight. Preflexion larvae of the two species are similar, butS. tome larvae can be distinguished from those ofS. guachancho by having small melanophores on the midbrain and a row of melanophores along the ventral midline of the lower jaw and isthmus. Flexion and postflexion larvae ofS. tome are more slender than those ofS. guachancho. Morphology and pigment patterns ofS. tome are similar to those ofS. borealis from the north Atlantic. whereasS. guachancho larvae are similar toS. barracuda in having a fusiform body, advanced position of the pelvic fins and a heavily pigmented tail region, but differ in having a fleshy tip on the lower jaw in postflexion and juvenile stages.

MicroRNAs (miRNAs), a family of endogenous small non-coding RNAs, are associated with the development of renal diseases. To clarify whether urinary miRNAs (UmiRNAs) can be used for the evaluation of renal disease, we examined the profiles of UmiRNAs in various renal diseases. We extracted miRNAs from urine specimens of 5 healthy controls and 71 patients with renal diseases, and we examined the correlation between clinical and histological parameters and the profile of UmiRNAs by microarray analysis. The urinary concentration of miRNAs increased in patients with renal disease compared with healthy controls, and the levels correlated with urinary protein and the degree of glomerular sclerosis. The microarray analysis detected 83–137 distinct UmiRNAs. We observed 80–99 % of the miRNAs in both the healthy controls and the renal disease patients. The majority of UmiRNAs displayed higher signal intensity in renal disease patients than in healthy controls, including 39 miRNAs exhibiting signal intensities 100 times greater than in healthy controls. A different pattern of UmiRNAs was observed in each type of renal disease. A comparison of renal tissue and UmiRNAs revealed that the sample profiles were similar and that their signal intensity was significantly correlated. This study demonstrated that UmiRNAs are correlated with renal pathological changes and that the profile of UmiRNAs presented different patterns corresponding to the type of renal disease. These results suggest that UmiRNAs can potentially be used as novel biomarkers for renal diseases.